Female-biased association of NOS2-c.1823C>T (rs2297518) with co-susceptibility to metabolic syndrome and asthma

Can J Physiol Pharmacol. 2023 Apr 1;101(4):200-213. doi: 10.1139/cjpp-2022-0334. Epub 2023 Jan 30.

Abstract

The nitric oxide (NO) pathway contributes to the pathogeneses of metabolic syndrome (MetS) and asthma. NOS2 encodes inducible-NO synthase, which is an important enzyme of the pathway, and its variations could affect the risk of asthma and MetS and thereby co-susceptibility to them. This study aims to estimate the association of NOS2-c.1823C>T with risk of asthma, MetS, and asthma with MetS condition (ASMetS), and with asthma stages: intermittent, mild, moderate, and severe asthma. The study included asthmatics (n = 555), MetS (n = 334), and ASMetS cases (n = 232) and 351 controls, which were genotyped by the PCR-RFLP method. The T allele was significantly associated with an increased risk of asthma and MetS in the sample population and females. CT genotype and CT+TT model were significantly associated with increased risk of ASMetS in females. A significant association between CT genotype and increased risk of ASMetS in the sample population and females was found in ASMetS versus MetS. In the sample population and among females, the T allele was significantly associated with severe asthma. The rs2297518 single nucleotide polymorphism of NOS2 contributes to the risk of MetS, asthma, and co-susceptibility to them, and this contribution may be stronger in females compared to males.

Keywords: SNP; iNOS; lung; metabolic disorder; nitric oxide pathway; p.Ser608Leu.

MeSH terms

  • Alleles
  • Asthma* / complications
  • Asthma* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Metabolic Diseases*
  • Metabolic Syndrome* / complications
  • Metabolic Syndrome* / genetics
  • Nitric Oxide Synthase Type II / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Nitric Oxide Synthase Type II
  • NOS2 protein, human